S155: PROGNOSTIC FACTORS FOR 3-YEAR MAJOR MOLECULAR RESPONSE MAINTENANCE IN CHRONIC MYELOID LEUKAEMIA PATIENTS IN THE EUROPEAN STOP KINASE INHIBITORS (EURO-SKI) TRIAL
Authors: Markus Pfirrmann, Francois-Xavier Mahon, Stéphanie Dulucq, Andreas Hochhaus, Panayiotis Panayiotidis, Antonio Almeida, Jiri Mayer, Henrik Hjorth-Hansen, Jeroen J. W. M. Janssen, Satu Mustjoki, Joaquín Martinez-Lopez, Hanne Vestergaard, Hans Ehrencrona, Veli Kairisto, Kateřina Machová Poláková, Franck Emmanuel Nicolini, Wolf-Karsten Hofmann, Joëlle Guilhot, Susanne Saussele, Johan Richter
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: The European stop kinase inhibitors (EURO-SKI) trial was set up to deepen the knowledge on successful cessation of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) patients with stable deep molecular response (DMR: BCR::ABL1 transcripts ≤0.01% on the International Scale, IS). The trial targeted on adult chronic-phase patients on TKI treatment in confirmed DMR for at least one year and under TKI treatment for at least 3 years. One goal of the trial was the investigation of prognostic factors affecting major molecular response (MMR: BCR::ABL1 ≤0.1% IS) maintenance after stop of TKI treatment. Aims: Prognostic factors associated with MMR maintenance 3 years after imatinib stop should be identified and validation be attempted. Methods: The analysis of prognostic factors focussed on patients with first-line imatinib treatment and without interferon-alpha pre-treatment. Candidate prognostic factors were age at diagnosis and at TKI discontinuation, duration of TKI treatment and of DMR before TKI discontinuation, time to DMR while receiving TKI, sex, and, despite reduced number of cases due to missing values, transcript type, spleen size below costal margin, platelet count, and percentage of blasts in peripheral blood at diagnosis. Logistic regression analysis was used to identify the variables with significant (p < 0.05) influence on MMR maintenance at 3 years. Validation of results was attempted in data of the STIM2 trial. Results: Of 868 patients pre-registered for the EURO-SKI trial, 140 patients failed eligibility criteria and were excluded. Of the remaining 728 patients, 52 patients had no data on molecular response at both times, at 6 and 36 months. Further 45 patients did not have imatinib as first-line TKI and another 121 patients were pre-treated with IFN. After removal of these 218 patients, 510 were left for prognostic analysis. At 36 months, 41% of 510 (95% CI: 37-46%) were still in MMR. In univariate regression, longer duration of TKI treatment (p=0.0014), longer duration of DMR while receiving TKI (p=0.0110), and fewer blasts (p=0.0137) were significantly associated with MMR maintenance at 36 months, see table. With transcript type, e14a2 (+e13a2) was more favourable than e13a2 alone (p=0.0051). Three alternative multiple logistic regression models were identified: a) Duration of TKI treatment (p=0.0043) plus blasts (p=0.0116), b) duration of TKI treatment (p=0.0163) plus transcript type (p=0.0047), and c) duration of DMR while receiving TKI (p=0.0149) plus time to DMR while receiving TKI (p=0.0261) plus blasts (p=0.0112). Due to correlations and different sample sizes, the 3 models were not statistically comparable. Data on MMR status at 36 months was available in 184 of 199 patients in the STIM2 trial. MMR was maintained in 45% (95% CI: 38-52%). Univariate significance was confirmed in all factors: Duration of TKI treatment (p=0.0087), duration of DMR while receiving TKI (p=0.0134), blasts (p=0.0291), and transcript type (p=0.0211), see table. Multiple models a) (p=0.0057 and 0.0447) and b) (p=0.0019 and p=0.0053) were confirmed but not model c). Summary/Conclusion: Four prognostic factors and 2 prognostic models for MMR maintenance at 36 months after TKI discontinuation were identified in the EURO-SKI trial and validated in the STIM2 trial, despite much smaller sample size in the latter. It is remarkable that blasts at diagnosis still played a role in good molecular responders, just as in survival of all patients in chronic phase. Next, differences in early and late loss of MMR and the suggestion of a prognostic score will be explored.Keywords: Prognosis, Chronic myeloid leukemia, Tyrosine kinase inhibitor, treatment-free remission